[Does clonidine modify the hypnotic effect of propofol?].

The administration of alpha 2-adrenoceptor agonists before the induction of anaesthesia leads to a significant reduction in the amount of anaesthetic medication required, probably due to an attenuation of haemodynamic stress responses in centrally mediated sympathicolysis. However, it is not yet known whether alpha 2-adrenoceptor agonists influence the hypnotic action of anaesthetics. Therefore, this study was performed to evaluate the influence of the alpha 2-adrenoceptor agonist clonidine on the potency and the duration of the hypnotic action of anaesthetic agents. METHOD. The study was approved by the local ethical committee. To study the effect of clonidine on the potency of propofol we determined the ED50 of propofol with and without clonidine pretreatment. To this end, 100 unpremedicated patients (ASA I or II) were randomly assigned to receive 4 micrograms/kg body weight clonidine or placebo, each of which was dissolved in 100 ml NaCl and infused over a period of 15 min starting 30 min before the induction of anaesthesia. According to the results of a pilot study, patients who had been treated with clonidine received either 0.25, 0.5, 0.75, 1 or 1.25 mg/kg propofol for anaesthesia induction. Patients in the placebo group received 0.5, 1, 1.5, 2 or 2.5 mg/kg propofol. The success of anaesthesia induction was evaluated clinically (eye opening on command, eyelid reflex). On the basis of these data the ED50 of propofol with and without clonidine pretreatment was calculated using the modified probit analysis according to Spearman and Kärber. The effect of clonidine on the duration of anaesthesia was compared in six groups of 10 patients each, who received 1, 1.5 or 2 mg/kg propofol for anaesthesia induction with and without prior clonidine treatment. RESULTS. In the placebo group a dose of 0.5 mg propofol per kg did not produce a hypnotic effect in any patient, while 2.5 mg propofol per kilogram of body weight was effective in all patients. In the clonidine group 0.25 mg propofol per kilogram of body weight had no hypnotic effect, while 1.25 mg propofol per kilogram of body weight was effective in all patients. Increasing the dose of propofol resulted in an increasing number of successful anaesthesia inductions in the placebo as well as in the clonidine group. According to these data, the ED50 of propofol with clonidine was calculated at 0.675 +/- 0.23 mg/kg with clonidine and 1.5 +/- 0.58 mg/kg without clonidine pretreatment. Increasing the dose of propofol did not result in a significant increase in the duration of anaesthesia (1 mg/kg: 260 +/- 114 s; 1.5 mg/kg: 270 +/- 103 s; 2 mg/kg: 295 +/- 152 s). However, premedication with clonidine almost doubled the duration of the hypnotic action of propofol (1 mg/kg: 457 +/- 239 s; 1.5 mg/kg: 501 +/- 249 s; 2 mg/kg: 582 +/- 254 s) (P < 0.01). CONCLUSION. According to these findings the administration of clonidine prior to anaesthesia induction significantly increases the potency and the duration of the hypnotic action of propofol. From our data we conclude that the influence of clonidine on the hypnotic action of anaesthetics is an important factor in the reduction of anaesthetic requirements observed after clonidine pretreatment.